Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacothe...Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future directions.PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis.Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation.Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation.The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis.Diuretics remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites.Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications.Despite initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated cirrhosis.Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality.Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting.Emerging evidence indicates that anticoagulation therapy reduces incidence and increases展开更多
Hepatic encephalopathy is a spectrum of reversible neuropsychiatric abnormalities,seen in patients with liver dysfunction and/or portosystemic shunting.One of the most debilitating complications of cirrhosis,encephalo...Hepatic encephalopathy is a spectrum of reversible neuropsychiatric abnormalities,seen in patients with liver dysfunction and/or portosystemic shunting.One of the most debilitating complications of cirrhosis,encephalopathy affects 30-45% of cirrhotics.In addition to significantly affecting the lives of patients and their caregivers,it is also associated with increased morbidity and mortality as well as significant utilization of health care resources.In this paper,we provide an overview on the pathophysiology,diagnosis,management and newer therapies of hepatic encephalopathy.展开更多
Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibi...Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.展开更多
Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of ...Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial "fingerprint",characterized by the reduced ratio of "good" to "potentially pathogenic" bacteria has recently been outlined,and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover,in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis(SBP),hepatic encephalopathy(HE),and,portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic,immune-modulating and anti-inflammatory activity,a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE,and also to prevent the development of SBP,to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality,triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease.展开更多
AIM： TO estimate the prevalence of small intestinal bacterial overgrowth （SIBO） in our geographical area （Western Sicily, Italy） by means of an observational study, and to gather information on the use of locally...AIM： TO estimate the prevalence of small intestinal bacterial overgrowth （SIBO） in our geographical area （Western Sicily, Italy） by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO.METHODS： Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome （IBS）; a total of 97 patients accepted to perform a breath test with lactulose （BTLact）, and those who had a positive test, received Rifaximin （Normix , Alfa Wassermann） 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated.RESULTS： Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with Rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS. CONCLUSION： SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a ＂breath test＂. Rifaximin may represent a valid approach to the treatment of SIBO.展开更多
AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; rang...AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.展开更多
The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic...The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.展开更多
Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestin...Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.展开更多
BACKGROUND Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis.However,few studies have investigated the effect of rifaximin in cirrhotic patie...BACKGROUND Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis.However,few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites.AIM To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism.METHODS A total of 75 cirrhotic patients with refractory ascites were enrolled in the study(50 in a rifaximin and 25 in a control group).Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics(19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics).All patients received conventional treatment for refractory ascites,while patients in the rifaximin group received oral rifaximin-α200 mg four times daily for at least 2 wk.The ascites grade,fasting weight,liver and kidney function,and inflammatory factors in the plasma were evaluated before and after treatment.In addition,the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment.The patients were followed for 6 mo.RESULTS Compared with the control group,the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin(P=0.011 and 0.009,respectively).The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group(P=0.048).The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group(P=0.024).The abundance of Roseburia,Haemophilus,and Prevotella was significantly reduced after rifaximin treatment,while the abundance of Lachnospiraceae_noname,Subdoligranulum,and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifa展开更多
基金Supported by The Division of Integrative Systems Medicine and Digestive Disease at Imperial College London receives financial support from the National Institute for Health Research(NIHR)Imperial Biomedical Research Centre(BRC)based at Imperial College Healthcare NHS Trust and Imperial College Londonfunded by the NIHR BRC
文摘Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future directions.PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis.Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation.Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation.The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis.Diuretics remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites.Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications.Despite initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated cirrhosis.Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality.Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting.Emerging evidence indicates that anticoagulation therapy reduces incidence and increases
文摘Hepatic encephalopathy is a spectrum of reversible neuropsychiatric abnormalities,seen in patients with liver dysfunction and/or portosystemic shunting.One of the most debilitating complications of cirrhosis,encephalopathy affects 30-45% of cirrhotics.In addition to significantly affecting the lives of patients and their caregivers,it is also associated with increased morbidity and mortality as well as significant utilization of health care resources.In this paper,we provide an overview on the pathophysiology,diagnosis,management and newer therapies of hepatic encephalopathy.
文摘Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.
文摘Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial "fingerprint",characterized by the reduced ratio of "good" to "potentially pathogenic" bacteria has recently been outlined,and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover,in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis(SBP),hepatic encephalopathy(HE),and,portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic,immune-modulating and anti-inflammatory activity,a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE,and also to prevent the development of SBP,to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality,triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease.
文摘AIM： TO estimate the prevalence of small intestinal bacterial overgrowth （SIBO） in our geographical area （Western Sicily, Italy） by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO.METHODS： Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome （IBS）; a total of 97 patients accepted to perform a breath test with lactulose （BTLact）, and those who had a positive test, received Rifaximin （Normix , Alfa Wassermann） 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated.RESULTS： Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with Rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS. CONCLUSION： SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a ＂breath test＂. Rifaximin may represent a valid approach to the treatment of SIBO.
文摘AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.
文摘The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.
文摘目的研究益生菌对肠易激综合征(irritable bowel syndrome,IBS)合并小肠细菌过度生长(small intestinal bacterial overgrowth,SIBO)的治疗效果。方法选择2012年1月-2013年8月我院诊断的IBS患者100例为研究对象,男性38例,女性62例,年龄(44.7±8.1)岁。所有患者均完成甲烷-氢呼气试验,将64例阳性者随机分为抗生素组(22例,利福昔明治疗)、微生态组(21例,双岐杆菌三联活菌胶囊治疗)及安慰剂组(21例,安慰剂治疗),比较3组患者治疗前后临床症状积分、小肠细菌过度生长转阴率、治疗有效率之间的差异。结果抗生素组(11.39±3.67 vs 4.96±1.19)与微生态组(11.38±3.46 vs 4.89±1.17)治疗前后的临床症状积分均明显改善(P<0.001);微生态组治疗后临床症状积分(4.89±1.17)、总有效率(85.71%)及SIBO转阴率(71.43%)与抗生素组(4.96±1.19,86.36%,72.73%)差异无统计学意义(P>0.05);抗生素组、微生态组治疗后临床症状积分、总有效率及转阴率与安慰剂组治疗后(10.23±3.43,28.57%,9.50%)差异均有统计学意义(P<0.05)。结论双歧杆菌三联活菌胶囊与利福昔明疗效同样确切,微生态制剂可以广泛用于IBS合并SIBO的治疗。
文摘Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.
基金Supported by the State Key Projects Specialized on Infectious Diseases,No.2017ZX10203202-004 and No.2017ZX10203202003008the Digestive Medical Coordinated Development Centre of the Beijing Municipal Administration of Hospitals,No.XXZ0303+1 种基金Beijing High-level Health Technicians,No.2013-03-073Beijing Municipal Administration of Hospitals’Ascent Plan,No.DFL20151602
文摘BACKGROUND Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis.However,few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites.AIM To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism.METHODS A total of 75 cirrhotic patients with refractory ascites were enrolled in the study(50 in a rifaximin and 25 in a control group).Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics(19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics).All patients received conventional treatment for refractory ascites,while patients in the rifaximin group received oral rifaximin-α200 mg four times daily for at least 2 wk.The ascites grade,fasting weight,liver and kidney function,and inflammatory factors in the plasma were evaluated before and after treatment.In addition,the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment.The patients were followed for 6 mo.RESULTS Compared with the control group,the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin(P=0.011 and 0.009,respectively).The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group(P=0.048).The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group(P=0.024).The abundance of Roseburia,Haemophilus,and Prevotella was significantly reduced after rifaximin treatment,while the abundance of Lachnospiraceae_noname,Subdoligranulum,and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifa
